The research proposed in this application is crucial in elucidating the neural effects of heroin self- administration within the medial prefrontal cortex, which is a region believed to be instrumental in controlling behavior induced by rewarding stimuli. Specific emphasis will be placed on mitogen-activated protein kinase (MARK) pathways. Because these proteins are important intracellular switches, findings from these studies will be crucial in directing future research examining targets downstream from MARK pathways. The microarray screening included in this proposal provides an initial investigation aimed at identifying promising targets for clinical use in treating opiate addiction. Through identification of changes in intracellular components that accompany opiate addiction, pharmacological treatments targeted towards eliminating these intracellular changes while precipitating minimal withdrawal can be developed. [unreadable] [unreadable] [unreadable]